Abstract |
In X-linked hypophosphatemia (XLH), serum fibroblast growth factor 23 (FGF23) is increased and results in reduced renal maximum threshold for phosphate reabsorption ( TmP), reduced serum inorganic phosphorus (Pi), and inappropriately low normal serum 1,25 dihydroxyvitamin D ( 1,25[OH]2 D) concentration, with subsequent development of rickets or osteomalacia. KRN23 is a recombinant human IgG1 monoclonal antibody that binds to FGF23 and blocks its activity. Up to 4 doses of KRN23 were administered subcutaneously every 28 days to 28 adults with XLH. Mean ± standard deviation KRN23 doses administered were 0.05, 0.10 ± 0.01, 0.28 ± 0.06, and 0.48 ± 0.16 mg/kg. The mean time to reach maximum serum KRN23 levels was 7.0 to 8.5 days. The mean KRN23 half-life was 16.4 days. The mean area under the concentration-time curve (AUCn ) for each dosing interval increased proportionally with increases in KRN23 dose. The mean intersubject variability in AUCn ranged from 30% to 37%. The area under the effect concentration-time curve (AUECn ) for change from baseline in TmP per glomerular filtration rate, serum Pi, 1,25(OH)2 D, and bone markers for each dosing interval increased linearly with increases in KRN23 AUCn . Linear correlation between serum KRN23 concentrations and increase in serum Pi support KRN23 dose adjustments based on predose serum Pi concentration.
|
Authors | Xiaoping Zhang, Erik A Imel, Mary D Ruppe, Thomas J Weber, Mark A Klausner, Takahiro Ito, Maria Vergeire, Jeffrey Humphrey, Francis H Glorieux, Anthony A Portale, Karl Insogna, Thomas O Carpenter, Munro Peacock |
Journal | Journal of clinical pharmacology
(J Clin Pharmacol)
Vol. 56
Issue 2
Pg. 176-85
(Feb 2016)
ISSN: 1552-4604 [Electronic] England |
PMID | 26073451
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2015 The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology. |
Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Biomarkers
- FGF23 protein, human
- Phosphorus
- Fibroblast Growth Factor-23
- burosumab
|
Topics |
- Adult
- Aged
- Antibodies, Monoclonal
(administration & dosage, pharmacokinetics, pharmacology)
- Antibodies, Monoclonal, Humanized
- Area Under Curve
- Biomarkers
- Bone and Bones
(metabolism)
- Familial Hypophosphatemic Rickets
(drug therapy)
- Female
- Fibroblast Growth Factor-23
- Humans
- Male
- Middle Aged
- Phosphorus
(blood)
- Young Adult
|